tbuckley/cabot-search huggingface dataset:
Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer
Authors: Yansong Lin, Shukui Qin, Hui Yang, Feng Shi, Aimin Yang, Xingmin Han, Bin Liu, Zhiyong Li, Qinghai Ji, Lijun Tang, Zhiyong Deng, Yong Ding, Wei Fu, Xianhe Xie, Linfa Li, Xiaohui He, Zhongwei Lv, Qingjie Ma, Zan Shen, Zhuming Guo, Zhendong Chen, Yali Cui, Jian Tan, Zairong Gao, Shanghua Jing, Keyi Lu, Xianyang Luo, Yuan Zhang, Yong Fang, Zhendong Li, Yizhuang Cheng, Shangtong Lei, Sha Luan, Guang Chen, Guihua Wang, Liqing Wu, Lingling Liu
Journal: Clinical Cancer Research (2023)

The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC.This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc.Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation.Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.
Effect of interval between neoadjuvant chemoradiotherapy and surgery on oncological outcomes in poor responders with locally advanced rectal cancer: a retrospective cohort study
Authors: Dakui Luo, Yufei Yang, Ruijia Zhang, Qingguo Li, Xinxiang Li
Journal: International Journal of Surgery (2023)

Background: The optimal interval from completion of neoadjuvant chemoradiotherapy (CRT) to surgery in locally advanced rectal cancer (LARC) remains controversial. It seems that delayed surgery is associated with an increase in pathological complete response rates. However, the prognostic effect of delayed surgery in poor responders is unclear. Materials and Methods: Patients with locally advanced mid- or distal rectal cancer undergoing neoadjuvant CRT followed by total mesorectal excision at a university teaching cancer center between June 2010 and December 2018 were retrospectively reviewed in this study. According to the tumor regression grade (TRG), poor responders (TRG2-3) to neoadjuvant CRT were selected for analyses. Patients were divided into the longer interval group (greater than 8 wk) and the shorter interval group (8 wk or less) based on the wait time from completion of neoadjuvant CRT therapy to surgery. Results: Among 916 eligible patients, 522 patients had a poor tumor response. There were 217 patients in the shorter interval group and 305 patients in the longer interval group. At the baseline, patients in the longer interval group were more likely to have T3 stage and positive vascular invasion. Compared with patients in the shorter interval group, patients in the longer interval group had significantly worse overall survival (OS) and disease-free survival (DFS) (log-rank test, OS: P=0.004, DFS: P<0.001). The 3-year DFS rates were 75.6 and 63.1% in the shorter interval group and the longer interval group, respectively. In the multivariate analysis, delayed surgery was associated with an increased risk of mortality (hazard ratio: 2.003, 95% CI: 1.233–3.253, P=0.005) and recurrence (hazard ratio: 1.555, 95% CI: 1.121–2.156, P=0.008). Conclusion: Patients who had a poor tumor response should be identified by restaging MRI and receive radical surgery in time, without a prolonged interval.
Making Sure Multiple Sclerosis Counts and Is Counted for All—An Update on Multiple Sclerosis Prevalence by Race and Ethnicity in the United States
Authors: Dalia L. Rotstein, Tirisham V. Gyang, Daniel Ontaneda
Journal: JAMA Neurology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Preoperative Evaluations Before Transplantation—Essential Tools, Not Obstacles
Authors: Larry A. Weinrauch, John A. D’Elia
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology
Authors: Giorgia Serena Gullotta, Donatella De Feo, Ekaterina Friebel, Aurora Semerano, Giulia Maria Scotti, Andrea Bergamaschi, Erica Butti, Elena Brambilla, Angela Genchi, Alessia Capotondo, Mattia Gallizioli, Simona Coviello, Marco Piccoli, Tiziana Vigo, Patrizia Della Valle, Paola Ronchi, Giancarlo Comi, Armando D’Angelo, Norma Maugeri, Luisa Roveri, Antonio Uccelli, Burkhard Becher, Gianvito Martino, Marco Bacigaluppi
Journal: Nature Immunology (2023)
Availability of Unique Device Identifiers for Class I Medical Device Recalls From 2018 to 2022
Authors: Maryam Mooghali, Joseph S. Ross, Kushal T. Kadakia, Sanket S. Dhruva
Journal: JAMA Internal Medicine (2023)

This cross-sectional study describes the inclusion of unique device identifier in recall notices for moderate- and high-risk medical devices in the US.
Preoperative Evaluations Before Transplantation—Essential Tools, Not Obstacles
Authors: Steven A. Wisel, Justin A. Steggerda, Irene K. Kim
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
E2EFP-MIL: End-to-end and high-generalizability weakly supervised deep convolutional network for lung cancer classification from whole slide image
Authors: Lei Cao, Jie Wang, Yuanyuan Zhang, Zhiwei Rong, Meng Wang, Liuying Wang, Jianxin Ji, Youhui Qian, Liuchao Zhang, Hao Wu, Jiali Song, Zheng Liu, Wenjie Wang, Shuang Li, Peiyu Wang, Zhenyi Xu, Jingyuan Zhang, Liang Zhao, Hang Wang, Mengting Sun, Xing Huang, Rong Yin, Yuhong Lu, Ziqian Liu, Kui Deng, Gongwei Wang, Mantang Qiu, Kang Li, Jun Wang, Yan Hou
Journal: Medical Image Analysis (2023)
Lipid metabolism around the body clocks
Authors: Volodymyr Petrenko, Flore Sinturel, Howard Riezman, Charna Dibner
Journal: Progress in Lipid Research (2023)

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage. Specifically, we focus on the molecular interactions between functional clockwork and biosynthetic pathways of major lipid classes comprising cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, and sphingomyelins. A growing body of epidemiological studies associate a socially imposed circadian misalignment common in modern society with growing incidence of metabolic disorders, however the disruption of lipid metabolism rhythms in this connection has only been recently revealed. Here, we highlight recent studies that unravel the mechanistic link between intracellular molecular clocks, lipid homeostasis and development of metabolic diseases based on animal models of clock disruption and on innovative translational studies in humans. We also discuss the perspectives of manipulating circadian oscillators as a potentially powerful approach for preventing and managing metabolic disorders in human patients.
Dealing with dramatic health care problems during times of natural disaster and armed conflict
Authors: Sami Alasfar, Wasim Zakaria, Khaled Haj Nasan, Abdul R. Zanabli, Fahd Al-Saghir, Ahmad Oussama Rifai, Valerie Luyckx, Lina Murad, Saleh Kaysi, Akram Al-Makki, Mohamed Sekkarie
Journal: Kidney International (2023)
Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial
Authors: Cihan Atila, Friederike Holze, Rakithan Murugesu, Nikki Rommers, Nina Hutter, Nimmy Varghese, Clara O Sailer, Anne Eckert, Markus Heinrichs, Matthias E Liechti, Mirjam Christ-Crain
Journal: The Lancet Diabetes & Endocrinology (2023)
Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials
Authors: Henry F. Duncan, Yoshifumi Kobayashi, Michaela Kearney, Emi Shimizu
Journal: Bioactive Materials (2023)

This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based 'fillings' that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other 'smart' restorations in VPT.
Viral dynamics of SARS-CoV-2 in immunocompromised patients
Authors: Andrea N. Utzon, Isik S. Johansen, Line L. Bang, Rune M. Pedersen, Thomas E. Andersen, Lone W. Madsen
Journal: Clinical Microbiology and Infection (2023)

Immunocompromised patients infected with SARS-CoV-2 have been shown to shed replicable virus for a prolonged period of time, and the duration of isolation can therefore be difficult to estimate. The objective of this study was to evaluate the viral load dynamic in non-hospitalized immunocompromised patients infected with SARS-CoV-2 and treated with monoclonal antibodies (mAbs) or antivirals.Oropharyngeal swabs for RT-PCR and viral culture were collected from 29 immunocompromised patients before treatment with mAbs or antivirals and at days 5 and 15 after treatment. Overall, 12 patients were infected with the subvariant Omicron BA.1, 12 with Omicron BA.2, two with the Delta variant and for three patients determination of the variant were inconclusive.Before treatment with mAbs or antivirals, 22 of 29 patients (76% [95% CI, 56-90]) shed replicative SARS-CoV-2. At day 5, 21 patients (72% [95% CI, 53-87]) still tested RT-PCR-positive, but for 14 patients (48% [95% CI, 29-67]) there were no replicative virus in culture. At day 15, 16 patients (55% [95% CI, 36-74%]) tested positive but only two patients (7% [95%CI, 1-23]) had replicative virus.Half of the patients in this cohort had no viable virus after 5 days and only two patients had replicative virus after 15 days. This could indicate that the current CDC recommendations of an isolation period of 20 days for immunocompromised patients infected with SARS-CoV-2 could be reduced, but larger studies are needed to estimate the isolation duration for immunocompromised patients.
Phylogenetic Comparative Analysis of Single-Cell Transcriptomes Reveals Constrained Accumulation of Gene Expression Heterogeneity during Clonal Expansion
Authors: Feng Chen, Zizhang Li, Xiaoyu Zhang, Peng Wu, Wenjing Yang, Junnan Yang, Xiaoshu Chen, Jian-Rong Yang
Journal: Molecular Biology and Evolution (2023)

Abstract In the same way that a phylogeny summarizes the evolutionary history of species, a cell lineage tree describes the process of clonal expansion, in which gene expression differences between cells naturally accrue as a result of stochastic partitioning and imperfect expression control. How is functional homeostasis, a key factor in the biological function of any population of cells, maintained in the face of such continuous accumulation of transcriptomic heterogeneity remains largely unresolved. To answer this question, we experimentally determined the single-cell transcriptomes and lineage relationships of up to 50% cells in single-HEK293–seeded colonies. Phylogenetic comparative analyses of the single-cell transcriptomes on the cell lineage tree revealed three lines of evidence for the constrained accumulation of transcriptome heterogeneity among cells, including rapid saturation of transcriptomic heterogeneity upon four cell divisions, reduced expression differences within subtrees closer to expression boundaries, and cofluctuations among genes. Our analyses showcased the applicability of phylogenetic comparative methods in cell lineage trees, demonstrated the constrained accumulation of transcriptomic heterogeneity, and provided novel insight into the functional homeostasis of cell populations.
Gender inequalities as contributors to dementia in Latin America and the Caribbean: what factors are missing from research?
Authors: Fabiana S Ribeiro, Lucía Crivelli, Anja K Leist
Journal: The Lancet Healthy Longevity (2023)

<h2>Summary</h2> The current knowledge of modifiable risk factors for dementia comes mainly from high-income countries. In Latin America and Caribbean countries, where the burden of gender and socioeconomic inequalities is greater than in high-income countries, the prevalence of dementia is also higher and disease onset is earlier, especially among women, even after adjustments for life expectancy. In this Personal View, we discuss socioeconomic modifiable risk factors for dementia established by previous studies and postulate further harmful and often hidden factors faced by women that might influence the gender-specific timing of onset and general prevalence of dementia. We emphasise some of the effects of gender roles, their direct and indirect effects on dementia, and how they disproportionately impact women. Finally, we highlight the importance of bringing hidden risk factors to open discussion to promote research with high-quality data and to encourage public policies to promote and preserve women's health.
Neuropathology of incidental Lewy body &amp; prodromal Parkinson’s disease
Authors: Thomas Koeglsperger, Svenja-Lotta Rumpf, Patricia Schließer, Felix L. Struebing, Matthias Brendel, Johannes Levin, Claudia Trenkwalder, Günter U. Höglinger, Jochen Herms
Journal: Molecular Neurodegeneration (2023)

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing. Methods Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD. Results Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons. Conclusions Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.
Increasing the margin of patient safety for periodontal and implant treatments: The role of human factors
Authors: Franck Renouard, Erell Renouard, Alexandra Rendón, Harold M. Pinsky
Journal: Periodontology 2000 (2023)

Abstract Early complications following periodontal and dental implant surgeries are typically attributed to technique or poor biological response, ignoring the possibility of the human element. Interestingly, significant experience is not correlated with increased success, whereas evidence supports the impact of clinical behavior on patient outcome. This is the result of errors, much like those scrutinized in other high‐risk technical fields, such as aviation. What can be surprising is that those who make these errors are very well acquainted with best practices. Given this, how is it possible for the conscientious practitioner to fail to apply protocols that are nonetheless very well known? Recently, the concepts of human and organizational factors have been translated to medicine, though dentistry has been slow to recognize their potential benefit. This review lists specific human factor behaviors, such as use of checklists and crew resource management, which might improve postsurgical outcome.
Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease
Authors: Zhihai Huang, J. Dedrick Jordan, Quanguang Zhang
Journal: Translational Neurodegeneration (2023)

Abstract Neurological conditions, including cognitive impairment and Alzheimer’s disease (AD), impose a huge burden on society, affecting millions of people globally. In addition to genetic factors, recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases. Early life adversity (ELA) has a profound impact on brain function and health later in life. In rodent models, exposure to ELA results in specific cognitive deficits and aggravated AD pathology. Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA. In this review, we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD. These discoveries suggest that ELA, especially at early postnatal stages, increases susceptibility to cognitive impairment and AD later in life. In terms of mechanisms, ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis, altered gut microbiome, persistent inflammation, oligodendrocyte dysfunction, hypomyelination, and aberrant adult hippocampal neurogenesis. Crosstalks among these events may synergistically contribute to cognitive impairment later in life. Additionally, we discuss several interventions that may alleviate adverse consequences of ELA. Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.